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J Gordon

Publications and source records attributed to J Gordon.

At least 55 records · Page 3Linked to original sources
PubMed2000

Video intervention/prevention assessment: a patient-centered methodology for understanding the adolescent illness experience.

OBJECTIVE: To better understand the issues and needs of adolescents with chronic health conditions, the Video Intervention/Prevention Assessment (VIA) integrates video technology with qualitative research methods to obtain a patient-centered perspective on illness and health care. METHODS: Young people with chronic disease are interviewed for condition-specific verbal reports (CSVRs) of their medical and psychosocial histories. Standardized health-related quality of life (HRQL) instruments are administered. Trained to use video camcorders, participants record visual narratives of their illness experiences. They document their daily lives, interview families and friends, and record personal monologues regarding their observations, behaviors, understandings, and beliefs about their disease. On completion of the visual narratives, HRQL is again evaluated. Verbal, scaled, and visual data are analyzed from three perspectives: medical, psychosocial, and anthropological. Data from the CSVRs, HRQLs, and visual narratives are triangulated to validate and enrich findings. RESULTS: Investigating the illness experience from the adolescent patient's perspective, the VIA method was pilot-tested with children and adolescents with asthma. As a research tool, VIA found environmental risk factors, medication adherence problems, and outcome-affecting illness beliefs and psychological states that were not identified by standard clinical tools. As an intervention, VIA showed that it may be an effective tool for health-related environmental surveys. Participants' condition-specific quality of life showed measurable improvement after the self-examination process of VIA. As communication, VIA made apparently counterproductive patient behaviors understandable by showing them in context with the adolescent's experience of illness and health care. VIA can enhance medical history-taking and management strategies, improve adolescents' self-management skills, and educate clinicians, families, and students of the health care professions about the realities of the adolescent living with a chronic health condition.

Adolescent↗
PubMed2000

Micro-environmental factors in the survival of human B-lymphoma cells.

Burkitt lymphoma (BL) cells retain a high inherent propensity to undergo apoptosis indicating that net growth of the tumour population in vivo is likely to be influenced profoundly by its micro-environment. Here we investigate micro-environmental factors that affect BL-cell survival in vitro. We show that survival, and consequently net production, of tumour cells is enhanced by autocrine factors and, to a greater extent, by paracrine factors provided by relevant stromal elements of the tumour (fibroblasts and follicular dendritic cells) and by macrophages. Promotion of BL-cell survival by paracrine elements was mediated by cell/cell contact and by short-range soluble factor(s). IL-4, IL-10 and TNF-alpha promoted, whereas TGF-beta1 inhibited, tumour-cell production. Macrophages engaged in phagocytosis of apoptotic BL cells were less effective than untreated macrophages in supporting net expansion of BL populations. These results suggest that the net production of tumour cells in BL is supported by multiple micro-environmental factors that modulate apoptosis.

Apoptosis↗
PubMed2000

CD40 ligand, Bcl-2, and Bcl-xL spare group I Burkitt lymphoma cells from CD77-directed killing via Verotoxin-1 B chain but fail to protect against the holotoxin.

Owing to its lineage and differentiation stage-restricted expression, CD77 has been mooted as a therapeutic target in Burkitt lymphoma (BL). The recognition that the globotriaosyl moiety of this neutral glycosphingolipid is a receptor for Escherichia coli-derived Verotoxin-1 (Shiga-Like Toxin-1) offers a potential delivery system for the attack. Here we show that CD77-expressing Group I BL cells which are normally susceptible to activation-induced death on binding Verotoxin-1 B chain are protected in the presence of CD40 ligand. Ectopic expression of either bcl-2 or bcl-xL also afforded resistance to the actions of the B chain. In total contrast, neither of the survival genes nor a CD40 signal - even when acting in concert - protected against killing mediated by the holotoxin. These findings indicate that while therapeutic modalities for CD77-expressing B cell tumors (which include follicular lymphoma) based on the use of Verotoxin-1 B chain might be compromised by the activation of endogenous or exogenous survival pathways, those exploiting the holotoxin should be left unscathed.

Antibodies, Monoclonal↗
PubMed2000

Signals sustaining human immunoglobulin V gene hypermutation in isolated germinal centre B cells.

Affinity maturation of antibody responses depends on somatic hypermutation of the immunoglobulin V genes. Hypermutation is initiated specifically in proliferating B cells in lymphoid germinal centres but the signals driving this process remain unknown. This study identifies signals that promote V gene mutation in human germinal centre (GC) B cells in vitro. Single GC B cells were cultured by limiting dilution to allow detection of mutations arising during proliferation in vitro. Cells were first cultured in the presence of CD32L cell transfectants and CD40 antibody (the 'CD40 system') supplemented with combinations of cytokines capable of supporting similar levels of CD40-dependent GC B-cell growth [interleukin (IL)-10 + IL-1beta + IL-2 and IL-10 + IL-7 + IL-4]. Components of the 'EL4 system' were then added to drive differentiation, providing sufficient immunoglobulin mRNA for analysis. Analysis of VH3 genes from cultured cells by reverse transcription-polymerase chain reaction (RT-PCR)-based single-strand conformation polymorphism indicated that the combination IL-10 + IL-1beta + IL-2 promoted active V gene mutation whereas IL-10 + IL-7 + IL-4 was ineffective. This was confirmed by sequencing which also revealed that the de novo generated mutations were located in framework and complementarity-determining regions and shared characteristics with those arising in vivo. Somatic mutation in the target GC B-cell population may therefore be actively cytokine driven and not simply a consequence of continued proliferation. The experimental approach we describe should facilitate further studies of the mechanisms underlying V gene hypermutation.

B-Lymphocytes↗
PubMed2000

CD5-positive and CD5-negative human B cells converge to an indistinguishable population on signalling through B-cell receptors and CD40.

Whether CD5 on B cells marks a subset functionally distinct from the conventional CD5 negative (CD5neg) adult population or is more an indicator of activation, remains contentious. Here we have investigated whether CD5 positive (CD5pos) and CD5neg B cells can be distinguished in terms of their response to surrogate signals aimed to model, in vitro, T-cell dependent (TD) and T-independent (TI) encounters with antigen in vivo: the predominantly CD5pos B-cell population found in cord blood, CD5 B cells positively selected from tonsils and their CD5neg counterparts, were compared. Neonatal B cells displayed a near-identical phenotype to that of adult CD5pos B cells, being characterized by uniform immunoglobulin M (IgM), immunoglobulin D (IgD), CD23 and CD44 coexpression. When cultured with anti-IgM maintained at high density on CD32-tranfected mouse L cells to model TI responses or on CD40 ligand (CD40L)-bearing L cells (with or without captured anti-IgM) to model TD encounters, DNA synthesis was stimulated to a similar extent in all three populations. Focusing on CD5 and CD23, we found that - although the signals delivered promoted distinct profiles of expression - under each condition of activation, the phenotypes that emerged for adult CD5pos and CD5neg B cells were remarkably similar. Neonatal B cells displayed a greater diminution in CD5 expression than adult CD5pos B cells following CD40 signals but otherwise the two populations again behaved similarly. The inclusion of interleukin-4 (IL-4) to cultures where cells were costimulated via surface (s)IgM and CD40 resulted in a complete loss of CD5 expression and a corresponding hyperexpression of CD23, irrespective of the population studied. The near-identical response of CD5pos and CD5neg B cells to surrogate TD or TI signals in vitro and their convergence to indistinguishable phenotypes is wholly supportive of CD5 being a fluctuating marker of activation rather than it delineating functionally distinct subsets.

Adult↗
PubMed2000

The Consortium of Graduate Medical Schools in Australia: formal and informal collaboration in medical education.

CONTEXT: In 1996-97 three Australian medical schools adopted 4-year graduate medical courses. The schools formed a consortium to establish common admissions processes and to collaborate on curriculum and staff development. OUTCOMES: ADMISSIONS: Outcomes in admissions included the construction of an entry test and agreement on common application procedures. Structured interviews and measures of prior tertiary performance were adopted in each school with some local variations. Formal structures were put into place to manage the development of the test and admissions procedures. OUTCOMES: CURRICULUM AND STAFF DEVELOPMENT: No formal structures were put into place for curriculum and staff development. While the advantages of common approaches were recognised, it was accepted that it was also important to generate local ownership and commitment to the new courses. Outcomes of educational consortia should not be judged solely by the nature of joint ventures but by the way in which membership of the consortium changes the priorities and practices within the institutions. Examples of the operation of this principle within the three schools include: use of visiting experts to refine and modify approaches to problem-based learning; use of staff from partner institutions to facilitate implementation of the courses; sharing information technology expertise; cooperation in the construction of feedback mechanisms, and sharing advice on fulfilling accreditation requirements. CONCLUSION: The Consortium has had an important impact on Australian medical education. There is a need for further analysis of the two methods of operation of the consortium, formal and informal, and their relation to its overall functioning.

Australia↗
PubMed2000

Strategic planning in medical education: enhancing the learning environment for students in clinical settings.

BACKGROUND: The 1999 Cambridge Conference was held in Northern Queensland, Australia, on the theme of clinical teaching and learning. It provided an opportunity for groups of academic medical educators to consider some of the challenges posed by recent changes to health care delivery and medical education across a number of countries. PURPOSE: This paper describes the issues raised by the practical challenges posed by the current environment and how they might be addressed in ways that could promote more effective learning in clinical settings. METHOD: A SWOT analysis is a tool that can help in forward planning by identifying the strengths, weaknesses, opportunities and threats presented by any situation. Our SWOT analysis was used to generate a list of items, from which we chose those most feasible and most likely to promote positive change. RESULTS: Twenty different issues were identified, with four of them chosen by consensus for further elaboration. The discussion gave rise to four main recommended strategies: ensuring that clinical teachers thoroughly understand the purpose and process of learning in clinical settings; equipping learners with 'survival skills'; making the best use of learning resources within different clinical environments and making judicious use of information technology to enhance learning efficiency. CONCLUSIONS: The four strategies were selected not only because of their inherent importance, but also because of their feasibility. Modest changes can motivate students to feel part of a clinical team and a 'community of practice' and enhance their capacity for self-regulated practice.

Clinical Clerkship↗
PubMed2000

Increased expression of CD23 in rheumatoid synovitis.

OBJECTIVE: Soluble (s)CD23 is a potent macrophage stimulator. High levels of this molecule have been reported in rheumatoid arthritis (RA) serum. We investigated the expression of CD23 and its ligands in rheumatoid synovial fluid and cells. METHODS: Levels of sCD23, and cellular expression of CD23 and its ligands CD21, CD11b, and CD11c were measured in synovial fluid (SF) of RA patients and in blood of RA patients and controls. RESULTS: SF contained higher levels of sCD23 than either rheumatoid or normal sera (median 4.8, 3.16,and 1.13 ng/ml respectively, p <0.01). Synovial CD23 was found to be expressed principally on macrophages. While little CD21 expression was detected, CD11b and CD11c were both expressed at high levels, particularly on macrophages. CONCLUSIONS: Soluble CD23 is present in high levels in RA synovial fluid. Macrophages appear to be the principal source. Macrophages also express ligands for sCD23, and may therefore also be the targets of this potent pro-inflammatory molecule.

Arthritis, Rheumatoid↗
PubMed2000

Effect of highly active antiretroviral therapy on the incidence of HIV-related cytomegalovirus retinitis and retinal detachment.

Cytomegalovirus retinitis (CMVR) is the most common intraocular infection encountered in ophthalmic practices. To assess the impact of highly active antiretroviral therapy (HAART) on the incidence of CMVR and subsequent retinal detachments, a retrospective review of the HIV+ patients seen at a single university and community-based practice between 1992-1993 (group 1), before the advent of protease inhibitors, was compared with the data obtained from October 1996 to October 1997 (group 2) and October 1997-1998 (group 3), after the widespread use of HAART. The incidence of CMVR and retinal detachment rates for each group was calculated and compared. Twenty five (2.6%) of 974 HIV+ patients in group 1 developed CMVR. Of these, four patients developed retinal detachment (16%). Group 2 had a total of 1084 HIV+ patients, 18 (1.7%) of whom developed CMVR, which indicates a 35% decline of the incidence of CMV retinitis at our institution (p = 0.052, Odds ratio = 0.533, Confidence interval 0.28-1.01) and three patients (20%) developed retinal detachment. Only 1 patient (0.07%) of 1274 patients in group 3 developed CMVR, which represents a 99% reduction since 1993 (p = 0.0000000456). We conclude that the incidence of CMVR at this institution has decreased significantly with the recent use of HAART therapy. This effect may be related to the aggressive use of HAART and associated immune recovery in this population of AIDS patients. In this small series, however, the rate of retinal detachment appeared unchanged, but was only observed in those individuals who were not on HAART or who had just recently started.

AIDS-Related Opportunistic Infections↗
PubMed2000

Childhood visual experience affects adult voluntary ocular motor control.

PURPOSE: To quantify the effects of childhood visual experience/chronic visual deprivation upon adult voluntary ocular motor control. METHODS: Eye movements of blind and sighted adults were elicited and videotaped in total darkness. The videotaped responses were digitized using an eye tracker, yielding data from 10 congenitally blind (infantile onset, blindness before age 1 year), 16 adventitiously blind, and 9 sighted persons. RESULTS: Multivariate analysis of variance, trend analyses and post hoc tests revealed that primary position fixational stability and consistency of return to primary position were lowest in the congenitally blind vs. the adventitiously blind group, and highest in the sighted. Duration of adventitious blindness reduced primary position stability but not consistency of return to primary position. Secondary position maximum amplitudes: congenitally blind mean, 14 degrees; adventitiously blind mean, 40 degrees; sighted mean, 47 degrees. Average velocity (a form of Main Sequence) increased significantly with amplitude in all three groups. CONCLUSIONS: Visual deprivation can greatly attenuate but does not abolish human voluntary eye movement. Adventitious blindness exerts minimal to profound effects, commensurate with age of vision loss.

Adaptation, Physiological↗
PubMed2000

Time patterns of sperm whale codas recorded in the Mediterranean Sea 1985-1996.

A distinctive vocalization of the sperm whale, Physeter macrocephalus (=P. catodon), is the coda: a short click sequence with a distinctive stereotyped time pattern [Watkins and Schevill, J. Acoust. Soc. Am. 62, 1485-1490 (1977)]. Coda repertoires have been found to vary both geographically and with group affiliation [Weilgart and Whitehead, Behav. Ecol. Sociobiol. 40, 277-285 (1997)]. In this work, the click timings and repetition patterns of sperm whale codas recorded in the Mediterranean Sea are characterized statistically, and the context in which the codas occurred are also taken into consideration. A total of 138 codas were recorded in the central Mediterranean in the years 1985-1996 by several research groups using a number of different detection instruments, including stationary and towed hydrophones, sonobuoys and passive sonars. Nearly all (134) of the recorded codas share the same "3+1" (/// /) click pattern. Coda durations ranged from 456 to 1280 ms, with an average duration of 908 ms and a standard deviation of 176 ms. Most of the codas (a total of 117) belonged to 20 coda series. Each series was produced by an individual, in most cases by a mature male in a small group, and consisted of between 2 and 16 codas, emitted in one or more "bursts" of 1 to 13 codas spaced fairly regularly in time. The mean number of codas in a burst was 3.46, and the standard deviation was 2.65. The time interval ratios within a coda are parameterized by the coda duration and by the first two interclick intervals normalized by coda duration. These three parameters remained highly stable within each coda series, with coefficients of variation within the series averaging less than 5%. The interval ratios varied somewhat across the data sets, but were highly stable over 8 of the 11 data sets, which span 11 years and widely dispersed geographic locations. Somewhat different interval ratios were observed in the other three data sets; in one of these data sets, the variant codas were produced by a young whale. Two sets of presumed sperm whale codas recorded in 1996 had 5- and 6-click patterns; the observation of these new patterns suggests that sperm whale codas in the Mediterranean may have more variations than previously believed.

Animal Communication↗
PubMed2000

Transdominant activity of human immunodeficiency virus type 1 Vpr with a mutation at residue R73.

The 96-amino-acid-long human immunodeficiency virus type 1 virion-encoded accessory protein Vpr is of particular interest, as this protein, which is found in association with viral particles, can exert a regulatory effect on both virus replication and host cell function. Evidently, Vpr, through interaction with several host regulatory proteins, can modulate transcription from the viral long terminal repeat promoter. Expression of Vpr in cells results in deregulation of cell proliferation during the cell cycle pathway at the G(2) stage. Vpr has unique structural features consisting of multiple functional domains. In this study, we have focused on the leucine/isoleucine-rich domain near the carboxyl terminus of Vpr at residue 73 (arginine) and have demonstrated that alterations at this residue result in ablation of transcriptional activity of Vpr and its ability to block cell cycle events at the G(2) stage. Interestingly, substitution mutations at R73 have resulted in a peptide with dominant negative activities on wild-type functions in transcription and host proliferation events. Results from in vitro and in vivo protein-protein interaction studies have revealed that functionally inactive mutant Vpr can be associated with wild-type protein, presumably through the N-terminal regions of the protein which have been shown to be important for Vpr oligomerization. Thus, it is likely that complexation of the mutant Vpr with wild-type protein functionally inactivates Vpr. The importance of these findings in light of the development of therapeutic strategies is discussed.

Arginine↗
PubMed2000

Timing of onset of antidepressant response with fluoxetine treatment.

OBJECTIVE: The purpose of this study was to assess the time until onset of antidepressant response with fluoxetine treatment. METHOD: The authors evaluated 182 outpatients with major depression who had a sustained acute response to fluoxetine treatment. The outpatients received 8 weeks of treatment with 20 mg/day of fluoxetine and were assessed biweekly with the 17-item Hamilton Depression Rating Scale. The onset of response was defined as a 30% decrease in score on the Hamilton depression scale that persisted and led to a 50% decrease by week 8. The Kaplan-Meier product limit and Cox regression analysis were used to model the relationship between relevant variables and time until onset of response. RESULTS: The authors found that at weeks 2, 4, and 6, the probabilities of having an onset of response (for responders) were 55.5%, 24.7%, and 9.3%, respectively. The cumulative probabilities of onset of response at each time point were 55.5%, 80.2%, and 89.5%. Neither demographics nor clinical characteristics of depression predicted time until initial response. CONCLUSIONS: These data suggest that more than half of eventual responders to fluoxetine treatment at 8 weeks start to respond by week 2; over 75% start to respond by week 4. Conversely, the lack of onset of response at 4-6 weeks was associated with about a 73%-88% chance that patients would not have an onset of response by 8 weeks.

Adolescent↗
PubMed2000

Human polyomavirus JCV and expression of myelin genes.

Myelin basic protein (MBP) is a major component of the myelin sheath of both the central and peripheral nervous systems. A number of neurological diseases in humans are associated with demyelination of the central and/or peripheral nervous systems, including multiple sclerosis and its variants such as acute disseminated encephalomyelitis (AD), acute hemorrhagic leukoencephalopathy, and idiopathic polyneuritis (Guilliame-Barre syndrome), as well as tropical spastic paraparesis (TSP), and progressive multifocal leukoencephalopathy (PML). Multiple sclerosis (MS) is perhaps the most common demyelinating disease and is one of great importance to the clinical neurologist. The underlying cause of the demyelination seen in multiple sclerosis patients is unknown. However, patients frequently have unusually high antibody titers to a number of common viruses, leading to speculation that viral infections may participate in the pathogenesis of MS. On the other hand, studies on maternal and paternal twins have suggested the involvement of genetic factors in the predisposition of an individual toward developing MS. PML, once a rare demyelinating disease of elderly patients with lymphoproliferative disorders, is now a much more common disease affecting patients of all ages due to the increasingly widespread use of immunosuppressive chemotherapy and the prevalence of AIDS. PML is the result of productive infection of oligodendrocytes, the myelin producing cells of the CNS, with the human polyomavirus, JCV. In this article, we have focused our attention on PML, and the role of JCV in disrupting myelin sheaths by affecting myelin basic gene expression, ultimately leading to demyelination.

Genes, Viral↗